DESCRIPTION (Investigator's Abstract): The in vivo panoramic imaging system developed during the original grant provides continuous brain PHi, cerebral blood flow, and NADH fluorescence data of the majority of the exposed cortex in the animal model used in this research. This imaging technology has facilitated consistent identification and characterization of the ischemic penumbra, the border zone region of reduced blood flow surrounding the core of dense ischemia or evolving infarction. As described in the Background Data, we have identified acidic foci within the ischemic penumbra. In an evolving infarction, it is postulated that part of the ischemic penumbra deteriorates leading to an increase in the size of the infarction. One of the hypothesis in this grant is that these acidic foci may play a critical role in the recruitment of the ischemic penumbra into infarction. Therefore, comprehending the pathophysiology of these acidic foci may lead to treatments which can reverse this process thereby reducing the degree of ischemic neuronal injury. The experiments outlined in this grant will first study whether the development of the acidic foci is initially due to perfusion or metabolic disturbances. It will then be detained whether enlargement of the infarction is due to expansion and coalescing of the acidic foci or rather expansion of the infarction at the periphery. The remainder of the experiments will examine the effect of various factors on the acidic foci including serum glucose concentrations, P0O2, systemic and extracellular brain pM, reperfusion, and brain temperature.